One of the major features of growth is the accretion of protein. During perinatal growth proteins may accumulate by enhanced rates of protein synthesis and/or reduced rates of protein degradation. Control of protein turnover during fetal and early postnatal growth may be regulated by hormonal and nutritional factors, some of which may be unique to the perinatal period. The long-term objectives of this proposal are to gain a more detailed understanding of factors regulating protein turnover in the perinatal period during altered physiological states which perturb fetal and early postnatal growth and to test the hypothesis that lysosomal proteolysis is relatively unimportant in fetal skeletal muscle. Both in vivo and in vitro techniques will be used to study protein turnover in the fat fetus following maternal caloric and protein deprivation, as well as in states of fetal insulin deficiency and excess. The influence of postnatal hypothyroidism and malnutrition on protein turnover will also be assessed. Previous studies suggest that lysomomal proteolysis is deficient in fetal muscle. Studies to provide further evidence for this hypothesis will include analysis of protein breakdown in vitro in muscle from fetal and newborn rats under conditions known to affect lysosomal proteolysis in the juvenile rat, such as fasting and nurtitional/hormonal omission from incubation medium. Subcellular distribution and immunocytochemical location of lysosomal enzymes in muscles from fetal vs. young adults will be determined. An attempt will be made to dissect the pathway of lysosomal enzyme biosynthesis and processing by using skeletal muscle in tissue culture from fetal vs. junvenile rats. These studies should improve our understanding of factors regulating protein turnover in the fetus and, as a corollary, of mechanisms controlling fetal growth. Fetal growth retardation in humans is a major problem and understanding what factors contribute to growth retardation and how they do so may eventually help reduce the frequency of intrauterine growth retardation in the human.